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Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

ABSTRACT: Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P=0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P=0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife.

SUBMITTER: Jennings JR

PROVIDER: S-EPMC5685165 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

Jennings J Richard JR Heim Alicia F AF Sheu Lei K LK Muldoon Matthew F MF Ryan Christopher C Gach H Michael HM Schirda Claudiu C Gianaros Peter J PJ

Hypertension (Dallas, Tex. : 1979) 20171016 6

Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain ...[more]

PMID: 29038202

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Project description:Aims/hypothesisThe aim of this randomised, crossover trial was to compare cognitive functioning and associated brain activation patterns during hypoglycaemia (plasma glucose [PG] just below 3.1 mmol/l) and euglycaemia in individuals with type 1 diabetes mellitus.MethodsIn this patient-blinded, crossover study, 26 participants with type 1 diabetes mellitus attended two randomised experimental visits: one hypoglycaemic clamp (PG 2.8 ± 0.2 mmol/l, approximate duration 55 min) and one euglycaemic clamp (PG 5.5 mmol/l ± 10%). PG levels were maintained by hyperinsulinaemic glucose clamping. Cognitive functioning was assessed during hypoglycaemia and euglycaemia conditions using a modified version of the digit symbol substitution test (mDSST) and control DSST (cDSST). Simultaneously, regional cerebral blood flow (rCBF) was measured in pre-specified brain regions by six H215O-positron emission tomographies (PET) per session.ResultsWorking memory was impaired during hypoglycaemia as indicated by a statistically significantly lower mDSST score (estimated treatment difference [ETD] -0.63 [95% CI -1.13, -0.14], p = 0.014) and a statistically significantly longer response time (ETD 2.86 s [7%] [95% CI 0.67, 5.05], p = 0.013) compared with euglycaemia. During hypoglycaemia, mDSST task performance was associated with increased activity in the frontal lobe regions, superior parietal lobe and thalamus, and decreased activity in the temporal lobe regions (p < 0.05). Working memory activation (mDSST - cDSST) statistically significantly increased blood flow in the striatum during hypoglycaemia (ETD 0.0374% [95% CI 0.0157, 0.0590], p = 0.002).Conclusions/interpretationDuring hypoglycaemia (mean PG 2.9 mmol/l), working memory performance was impaired. Altered performance was associated with significantly increased blood flow in the striatum, a part of the basal ganglia implicated in regulating motor functions, memory, language and emotion.Trial registrationNCT01789593, clinicaltrials.gov FUNDING: This study was funded by Novo Nordisk.

Project description:Background Genome-wide association studies have identified >1000 genetic variants cross-sectionally associated with blood pressure variation and prevalent hypertension. These discoveries might aid the early identification of subpopulations at risk of developing hypertension or provide targets for drug development, amongst other applications. The aim of the present study was to analyze the association of blood pressure-associated variants with long-term changes (10 years) in blood pressure and also to assess their ability to predict hypertension incidence compared with traditional risk variables in a Swedish population. Methods and Results We constructed 6 genetic risk scores (GRSs) by summing the dosage of the effect allele at each locus of genetic variants previously associated with blood pressure traits (systolic blood pressure GRS (GRSSBP): 554 variants; diastolic blood pressure GRS (GRSDBP): 481 variants; mean arterial pressure GRS (GRSMAP): 20 variants; pulse pressure GRS (GRSPP): 478 variants; hypertension GRS (GRSHTN): 22 variants; combined GRS (GRScomb): 1152 variants). Each GRS was longitudinally associated with its corresponding blood pressure trait, with estimated effects per GRS SD unit of 0.50 to 1.21 mm Hg for quantitative traits and odds ratios (ORs) of 1.10 to 1.35 for hypertension incidence traits. The GRScomb was also significantly associated with hypertension incidence defined according to European guidelines (OR, 1.22 per SD; 95% CI, 1.10‒1.35) but not US guidelines (OR, 1.11 per SD; 95% CI, 0.99‒1.25) while controlling for traditional risk factors. The addition of GRScomb to a model containing traditional risk factors only marginally improved discrimination (Δarea under the ROC curve = 0.001-0.002). Conclusions GRSs based on discovered blood pressure-associated variants are associated with long-term changes in blood pressure traits and hypertension incidence, but the inclusion of genetic factors in a model composed of conventional hypertension risk factors did not yield a material increase in predictive ability.

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Project description:Numerous studies of insight problem solving are focused on both the control and storage systems of working memory. We obtained contradictory data about how working memory systems are involved in insight problem solving process. We argue that measuring the dynamics of the control system and storage systems through the course of problem solving can provide a more refined view on the processes involved, as a whole, and explain the existing controversies. We theorize that specific insight mechanisms require varying working memory capacities at different stages of the problem solving process. Our study employed a dual task paradigm to track the dynamics of working memory systems load during problem solving by measuring the reaction time in a secondary probe-task during different stages of problem solving. We varied the modality (verbal, visual) and the complexity of the probe-task during insight and non-insight problem solving. The results indicated that the dynamics of working memory load in insight problems differs from those in non-insight problems. Our first experiment shows that the complexity of the probe-task affects overall probe-task reaction times in both insight and non-insight problem solving. Our second experiment demonstrates that the solution of a non-insight problem is primarily associated with the working memory control system, while insight problems rely on relevant storage systems. Our results confirm that insight process requires access to various systems of working memory throughout the solution. We found that working memory load in non-insight problems increases from stage to stage due to allocation of the attentional control resources to interim calculations. The nature of the dynamics of working memory load in insight problems remains debatable. We claim that insight problem solving demands working memory storage during the entire problem solving process and that control system plays an important role just prior to the solution.

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Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

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Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

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